Page Metadata

Item Metadata

In harsh conditions Caenorhabditis elegans arrests development to enter a nonaging,
resistant diapause state called the dauer larva. Olfactory sensation modulates the
TGF-β and insulin-like signaling pathways to control this developmental decision. The
dauer pheromone is required for formation of dauer larvae. This thesis shows that
bacterial pathogenesis is an input into dauer formation in addition to the known inputs of
starvation, overcrowding and high temperature. This was first suggested by the overabundance
of innate immunity genes found in a screen for novel synthetic dauer
formation mutants. A total of 21 genes were identified in this screen, only one of which,
srh-100, was previously identified to influence dauer formation. This work also
characterizes new genes and functions that define early, middle, and late steps in the
dauer pathway. Epistasis analysis and a GFP-tagged reporter places DAF-25 (abnormal
DAuer Formation) function in the sensory cilia. DAF-25 was shown to be required for
DAF-11 cilia localization as well as proper olfaction to various cues. daf-25 and daf-11
mutants have similar phenotypes and epistatic order. Intraflagellar transport is not
defective in daf-25 mutants although the ciliary localization of DAF-25 itself is altered in
a mutant that is defective in retrograde IFT. A Daf-c enhancing mutant originally isolated
as a double mutant with a novel daf-2 allele was also identified. m708 is allelic with sdf-9
(Synthetic Dauer Formation). Epistasis analysis and allele-specific interactions place it in
the daf-2 pathway as a possible DAF-2 interactor. The molecular lesion in m708 was
identified to be an insertion of the mariner transposon Cemar1. This is the first identified
hopping event described for this transposon family, the largest in C. elegans. Finally, zip-
5 (initially identified as a candidate DAF-16/FOXO target by serial analysis of gene
expression) was shown to be a basic-leucine zipper transcription factor (bZIP) that is
down regulated in a daf-2 background. zip-5 mutants show an extension of life span that
is dependent on SKN-1, a bZIP-like transcription factor. ZIP-5 expression is dependant
on the longevity-associated DAF-16 transcription factor and the zip-5 GATA binding
sites.